P
US9650376B2ActiveUtilityPatentIndex 81

Imidazo(4,5-B) pyridin-2-yl amides as KV7 channel activators

Assignee: KNOPP BIOSCIENCES LLCPriority: Mar 15, 2013Filed: Mar 17, 2014Granted: May 16, 2017
Est. expiryMar 15, 2033(~6.7 yrs left)· nominal 20-yr term from priority
Inventors:RESNICK LYNNTOPALOV GEORGE TBOYD STEVEN ABELARDI JUSTIN KFLENTGE CHARLES AHALE JAMES SHARRIED SCOTT SMARESKA DAVID AZHANG KAIHEAP CHARLES RHADDEN MARKCUI WENGEDECORNEZ HÉLÈNELIU SHUANG
C07D 519/00C07D 471/04
81
PatentIndex Score
8
Cited by
22
References
23
Claims

Abstract

Compounds represented by formula 1 can be potent and/or partially selective for the Kv7.2/7.3 heteromultimer. They may be useful in treating disorders related to seizures, pain, neurotransmitter release, etc.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A compound represented by a formula: 
       
         
           
           
               
               
           
         
         wherein L is CH 2 , CF 2 , CHCH 3 , CH 2 CH 2 , C 3 H 6 , CH 2 O, C 2 H 4 O, or C 3 H 6 O with the O of CH 2 O, C 2 H 4 O, or C 3 H 6 O bonded with R 1 ; 
         wherein R 1  is optionally substituted C 1-2  alkyl, optionally substituted C 5-10  cycloalkyl, optionally substituted C 1-12  —O-alkyl, optionally substituted C 6-10  aryl, optionally substituted C 6-10  —O-aryl, or optionally substituted C 2-9  heterocyclyl, wherein the optional substituents of R 1  are independently R A , F, Cl, CN, OR A , CF 3 , NR A R B , COR A , CO 2 R A , OCOR A , NR A COR B , CONR A R B , wherein R A  and R B  are independently H or C 1-12  alkyl; 
         wherein R 2  is optionally substituted C 2-4  acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C 6-10  aryl, or optionally substituted C 2-9  heterocyclyl, wherein the optional substituents of R 2  are independently F, Cl, Br, I, CN, C 1-6  alkyl, C 1-6  —O-alkyl, C 1-6  alkylamine, C 1-6  aminoalkyl, C 1-6  aminoacyl, C 1-6  alkylthio, or C 1-6  alkylsulfonyl; 
         wherein R 3 , R 4 , and R 5  are independently H, F, Cl, Br, I, CN, optionally substituted C 1-12  alkyl, optionally substituted C 1-12  —O-alkyl, optionally substituted C 2-9  heterocyclyl, optionally substituted C 6-10  aryl, optionally substituted C 2-9  —O-heterocyclyl, optionally substituted C 6-10  O-aryl, optionally substituted C 1-12  acylamino, optionally substituted C 1-12  aminoacyl, or optionally substituted C 1-12  aminoalkyl, wherein the optional substituents of R 3 , R 4 , or R 5  are independently F, Cl, Br, I, CN, C 1-6  alkyl, C 1-6  —O-alkyl, C 1-6  alkylamine, C 1-6  aminoalkyl, C 1-6  aminoacyl, C 1-6  acylamino, C 1-6  alkylthio, or C 1-6  alkylsulfonyl. 
       
     
     
       2. The compound of  claim 1 , wherein R 2  is optionally substituted C 4 H 9 , optionally substituted cyclobutyl, optionally substituted C 6-10  aryl, or optionally substituted C 2-9  heterocyclyl. 
     
     
       3. The compound of  claim 2 , wherein R 2  is optionally substituted C 4 H 9 , or optionally substituted cyclobutyl. 
     
     
       4. The compound of  claim 2 , wherein R 2  is optionally substituted phenyl, or optionally substituted C 2-9  heterocyclyl. 
     
     
       5. The compound of  claim 1 , wherein R 1  is optionally substituted phenyl. 
     
     
       6. The compound of  claim 1 , wherein R 1  is optionally substituted C 1-2  alkyl. 
     
     
       7. The compound of  claim 1 , wherein R 1  is optionally substituted cyclopentyl or optionally substituted cyclohexyl. 
     
     
       8. The compound of  claim 1 , wherein R 1  is C 2-4  —O-alkyl. 
     
     
       9. The compound of  claim 1 , wherein R 1  is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl. 
     
     
       10. The compound of  claim 1 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
       11. The compound of  claim 1 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
       12. The compound of  claim 1 , wherein R 3  is CF 3 , Cl, CN, OCH 3 , or H. 
     
     
       13. The compound of  claim 12 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
       14. The compound of  claim 1 , wherein R 4  is CH 3 , CF 3 , Cl, or H. 
     
     
       15. The compound of  claim 14 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
       16. A compound represented by a formula: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       17. A pharmaceutical dosage form comprising a compound of  claim 1 . 
     
     
       18. A method of treating a disorder associated with a Kv7 potassium channel activator comprising administering an effective amount of a compound of  claim 1  to a mammal in need thereof, wherein the disorder is epilepsy, pain or migraine. 
     
     
       19. The method of  claim 18 , wherein the disorder is epilepsy, neuropathic pain, inflammatory pain, persistent pain, cancer pain, postoperative pain or migraine. 
     
     
       20. A method of treating a disorder associated with a Kv7 potassium channel activator comprising administering an effective amount of a compound of  claim 16  to a mammal in need thereof, wherein the disorder is epilepsy, pain or migraine. 
     
     
       21. The method of  claim 20 , wherein the disorder is epilepsy, neuropathic pain, inflammatory pain, persistent pain, cancer pain, postoperative pain or migraine. 
     
     
       22. A method of activating a Kv7 potassium channel comprising administering an effective amount of a compound of  claim 1  to a mammal in need thereof. 
     
     
       23. A method of activating a Kv7 potassium channel comprising administering an effective amount of a compound of  claim 16  to a mammal in need thereof.

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